In order to assess the role of the thymus in the acquisition of the T cell self-MHC specific repertoire. The MHC specificity of cytotoxic precursor T cells differentiating within thymuses engrafted into athymic nude mice was determined. The results demonstrated that cytotoxic T lymphocytes from such engrafted thymuses recognized TNP in association with thymic MHC determinants in various haplotype combinations of thymus graft and nude host. In contrast, cytotoxic T lymphocytes from the spleens of these same thymus grafted nude mice recognized TNP on both nude host and thymic MHC determinants. These results are consistent with the thymus being one site which determines MHC restrictions of T cell self recognition, while there exist other factors in this experimental model which have determined the host-restricted MHC specific repertoire observed in the spleens of thymus engrafted nude mice.